Acne vulgaris is a chronic disorder of the pilosebaceous follicles (apparatus) characterized by comedones (blackheads), papules, pustules, cysts, nodules, and often scars, that appear on the most visible areas of the skin (e.g., the face, chest, back, neck, and upper arms). The pilosebaceous apparatus is largely under the control of endogenous hormones (mainly androgens) which are present in unusually high concentrations in the blood during adolescence and puberty, giving rise to an excessive production of sebum. The condition may worsen by a simultaneous increase in the rate of keratinization of the skin""s horny layer (the stratum comeum). As the horny cells proliferate, they can form an occlusive plug or comedone which coupled with the increased production of the sebum, represents an ideal medium for the proliferation of the skin resident strains, such as the Gram positive anaerobic bacterium, Propionibacterium acnes. Eventually, the plugged follicles rupture and allow the discharge of their contents, causing local swelling and inflammation. The exposed follicles may darken from the deposition of pigment from damaged cells in the deeper layer of skin. In severe cases, acne can lead to hospitalization of the patient, extensive discomfort, and long term scarring of the skin.
There are numerous treatments available for treating acne. Typically, acne is treated with topical formulations in the form of creams, gels, emulsions or lotions that contain selected agents. These agents include hormones or hormone agonists and antagonists (EP A1 0 563 813 and U.S. Pat. No. 5,439,923), antimicrobial agents (U.S. Pat. No. 4,446,145, GB 2,088,717, GB 2,090,135, GB 1,054,124, U.S. Pat. No. 5,409,917), salicylic acid (U.S. Pat. No. 4,514,385, U.S. Pat. No. 4,355,028, EP A1 0 052 705, FR-A 2,581,542, and FR-A 2,607,498). The problems associated with topical treatment of acne with creams, gels, emulsions and lotions include, e.g., the lack of precision of the application of the cream, gel, emulsion or lotions and the associated lack of control over precise doses to the target site. The application of a cream, gel, emulsion or lotion typically results in the exposure of an area considerably in excess of that covered by the acne, thereby exposing normal healthy skin to the anti-acne formulation. In addition, creams, gels, emulsions and lotions are messy and inconvenient.
Oral administration of anti-acne agents is currently provided for severe cases of acne. These are reviewed in xe2x80x9cAcne, A Review of Optimum Treatmentxe2x80x9d by Sykes N. I. and Webster G. F in Drugs 48, 59-70 (1994). Numerous side-effects have been described using oral administration of anti-acne drugs. For example, isotretinoin, which is a derivative of vitamin A has associated risks of teratogenicity and may be a risk for women of childbearing age. Oral administration of antibiotics suited for treating acne may induce the appearance of adverse effects which include abdominal cramps, black tongue, cough, diarrhea, fatigue, irritation of the mouth and other undesirable symptoms.
Salicylic acid in the form of a tacky hydrophilic gel dressing (U.S. Pat. No. 5,258,421) and in combination with pantothenic acid or pantothenic acid derivative in a cleansing pad (PCT WO 93/21899) has been used for treating acne. In addition, a patch containing cephalosporin has been described in U.S. Pat. No. 5,409,917 for the treatment of acne using a method for making nicotine patches. Since the patch was not optimized for the special circumstances associated with acne including optimizing the anti-acne agent content and placement of the patch at multiple locations on exposed skin such as the face, the patch has not been adopted as an anti-acne formulation delivery modality.
FDA regulations (e.g., 21 C.F.R. Chapter 1, Section 333, Subpart D-Topical Acne Drug Products, Apr. 1, 2000 Edition) regulate what components (i.e., xe2x80x9cactive ingredientsxe2x80x9d), in a specified amount, may be described as treating acne (i.e., contains a topical acne drug). In order to follow FDA regulations, therefore, only a select number of active ingredients that are able to treat acne, in a specified amount, may be included in an adhesive patch when the patch is described as treating acne. Consequently, it is difficult to manufacture an adhesive patch that includes a topical acne drug, while at the same time maintaining (a) the solubility and stability of the active ingredients in the therapeutic formulation, (b) the pressure sensitive adhesive properties of the therapeutic formulation, and (c) following FDA regulations.
Several adhesive patches, drug dispensing devices, electrodes, and bandages have been disclosed for applying salicylic acid and/or sulfur to skin. See, e.g., U.S. Pat. Nos. 6,096,334; 6,096,033; 5,741,510; 5,536,263; 4,675,009; 4,307,717; and 4,274,420; which are all commonly assigned to Lec Tec Corporation. U.S. Pat. No. 4,274,420 discloses an electrode for use in monitoring and stimulation medical applications. The electrode includes a connector plug and a skin-interfacing substrate material. The substrate material can include salicylic acid in 17.8 wt. % (see, Example 2). The reference, however, does not disclose or suggest that the electrode can be used to treat acne. In addition, the reference does not disclose or suggest that salicylic acid can be present in the amount permitted by the FDA (e.g., 0.5 wt. % to 2.0 wt. % of the substrate). As such, the amount of salicylic acid disclosed therein does not comply with FDA regulations for topical acne drugs. See, 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, Apr. 1, 2000 Edition. Additionally, the backing is not disclosed as being treated with a sizing agent.
U.S. Pat. No. 4,307,717 discloses a bandage that includes a backing element and a substrate attached to the backing element. The substrate includes a matrix that includes a medicament. It is disclosed that the medicament can be a keratolytic agent such as salicylic acid or an antipruritic agent such as sulfur. However, the amount of salicylic acid or sulfur that can be employed in the matrix or substrate is not disclosed. The reference does not disclose or suggest that the bandage can be used to treat acne. In addition, the reference does not disclose or suggest that salicylic acid or sulfur can be present in the amount permitted by the FDA (e.g., 0.5 wt. % to 2.0 wt. % of the substrate or 3.0 wt. % to about 10.0 wt. % of the substrate, respectively). See, 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, Apr. 1, 2000 Edition. Additionally, the backing is not disclosed as being treated with a sizing agent.
U.S. Pat. No. 4,675,009 discloses a drug dispensing device (e.g., an adhesive skin reservoir) for the transdermal delivery of a medicament. The drug dispensing device includes a backing element and a substrate attached to the backing element. The substrate includes a medicament wherein the medicament can be a keratolytic agent such as salicylic acid (see, col. 3, line 66) or an antipruritic agent such as sulfur. The salicylic acid can be present in 8-20% of the substrate (see, Example 20). The amount of sulfur that can be employed in the substrate is not disclosed. The reference does not disclose or suggest that the drug dispensing device can be used to treat acne. In addition, the reference does not disclose or suggest that salicylic acid or sulfur can be present in the amount permitted by the FDA (e.g., 0.5 wt. % to 2.0 wt. % of the substrate or 3.0 wt. % to about 10.0 wt. % of the substrate, respectively). See, 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, Apr. 1, 2000 Edition. Additionally, the backing is not disclosed as being treated with a sizing agent.
U.S. Pat. Nos. 5,536,263 and 5,741,510 disclose an adhesive patch for applying medication to the skin. The patch includes a backing and a hydrocolloidal gel located on and in the backing. The gel includes a pressure-sensitive adhesive and a medicament. The medicament can be a keratolytic agent such as salicylic acid (see, col. 5, lines 35-36). The salicylic acid can be present in 4.1 wt. % (see, Example 46). The reference does not disclose or suggest that the adhesive patch can be used to treat acne. In addition, the reference does not disclose or suggest that salicylic acid can be present in the amount permitted by the FDA (e.g., 0.5 wt. % to 2.0 wt. % of the substrate). As such, the amount of salicylic acid disclosed therein does not comply with FDA regulations for topical acne drugs. See, 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, Apr. 1, 2000 Edition. Additionally, the backing is not disclosed as being treated with a sizing agent.
U.S. Pat. Nos. 6,096,333 and 6,096,334 disclose adhesive patches for applying medication to the skin. The patch includes a backing layer and a hydrophilic pressure-sensitive adhesive reservoir that includes a medicament. The medicament can be a keratolytic agent such as salicylic acid (see, col. 5, line 41). The salicylic acid can be present in 4.1 wt. % (see, Example 46). The references do not disclose or suggest that the adhesive patches can be used to treat acne. In addition, the references do not disclose or suggest that salicylic acid can be present in the amount permitted by the FDA (e.g., 0.5 wt. % to 2.0 wt. % of the substrate). As such, the amount of salicylic acid disclosed therein does not comply with FDA regulations for topical acne drugs. See, 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, Apr. 1, 2000 Edition. Additionally, the backing is not disclosed as being treated with a sizing agent.
The adhesive patches, drug dispensing devices, electrodes, and bandages disclosed in, e.g., U.S. Pat. Nos. 6,096,334; 6,096,033; 5,741,510; 5,536,263; 4,675,009; 4,307,717; and 4,274,420 have experienced success in applying and/or delivering medication to the skin. There exist several drawbacks, however, in the use of these adhesive patches, drug dispensing devices, electrodes, and bandages for delivering salicylic acid, in the amount permitted by the FDA, to treat acne or pimples. Specifically, the use of salicylic acid permitted by the FDA for acne medications has resulted in a less than desirable overall yield of product, a less than desirable xe2x80x9choldoutxe2x80x9d of therapeutic formulation on the backing, and a more than desirable degree of penetration of the therapeutic formulation in the backing.
U.S. Pat. No. 5,976,565 discloses a device for the topical treatment of acne. The device requires the presence of at least two agents suited for treating acne. See, e.g., col. 2, lines 36-37. The patch disclosed therein includes a release layer and at least one adhesive polymeric matrix layer located between the backing film and the release layer. As such, the adhesive polymeric matrix layer is not disclosed as being embedded or partially embedded in the backing film.
Many adhesive patches are manufactured or produced, for example, by mixing an ointment or gel in a mixer, then expelling the ointment or gel in a fluid state from the mixer onto the exposed front surface of a backing sheet. The fluid ointment or gel is then spread over the exposed surface of the backing sheet using an appropriate direct coating technique, such as knife-over-roll. This method of application allows the ointment or gel to penetrate a substantial portion of the backing sheet before it solidifies. However, if the fluid ointment or gel penetrates the backing too rapidly, it is possible for the ointment or gel to penetrate through the entire thickness of the backing before solidifying. Complete penetration of the ointment or gel through the backing results in the back side of the backing having a tacky surface. A tacky back side of the backing is unacceptable in that it may cause problems with further processing, such as die cutting or packaging, that is required to produce a finished product, and because it is an unattractive feature to the product consumer. Controlling the rate of penetration, such that the gel or ointment has solidified after it has begun to penetrate the backing, but before it has passed completely through the backing, or controlling the depth to which the ointment or gel will easily penetrate before solidifying, has been a persistent challenge.
There is a need therefore for methods and devices for treating patients with acne that have minimum adverse effects, have maximum efficacy, may be simple and comfortable to use, administers to the skin an effective and known amount of a topical acne drug, and complies with FDA regulations. The device will preferably be an adhesive patch that effectively controls the rate of penetration and/or effectively controls the depth to which the ointment or gel will penetrate before solidifying.
The present invention provides a water insoluble, protective, adhesive patch useful for treating or preventing acne or a pimple. The patch can prevent infections associated with acne or a pimple. The patch administers to the skin an effective and known amount of a topical acne drug. The patch maintains the adhesiveness of the adhesive and the stability of the topical acne drug over a prolonged period of time typically experienced in the manufacturing, packaging, shipping, and/or the storage of the patch. The topical acne drug, solvent, and pressure sensitive adhesive are positioned on at least a portion of the adhesive patch, in at least a portion of the adhesive patch, or on and in at least a portion of the adhesive patch. Preferably, the topical acne drug, solvent, and pressure sensitive adhesive are partially embedded in at least a portion of the adhesive patch. Additionally, the patch complies with FDA regulations (e.g., 21 C.F.R. Chapter 1, Section 333, Subpart D- Topical Acne Drug Products, Apr. 1, 2000 Edition). The adhesive patch of the present invention can include a gel that is not water-based. The adhesive patch includes a backing that is treated with a hydrophobic sizing agent (e.g., a fluorocarbon solution, silicone, or a combination thereof). The use of such backing prevents immediate wick through and maintains the hydrogel from penetrating the backing too quickly. In addition, the use of such backing provides a patch with a higher yield improvement and superior holdout properties. The use of such backing also obviates the need for a backing liner or a release liner. In such an embodiment, the adhesive patch can exist as a self wound adhesive patch.
The present invention provides an adhesive patch. The adhesive patch includes a flexible backing having a front side and a back side. A therapeutic formulation is positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing. At least a portion of the backing is treated with a hydrophobic sizing agent such that the portion of the backing that is treated with the hydrophobic sizing agent has a surface energy of about 20 dynes/cm2 to about 65 dynes/cm2. The therapeutic formulation includes a topical acne drug, a solvent that dissolves the topical acne drug, and a pressure sensitive adhesive.
The present invention also provides for another adhesive patch. The adhesive patch includes a flexible backing having a front side and a back side. A therapeutic formulation is positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing. At least a portion of the backing is treated with a hydrophobic sizing agent such that the portion of the backing treated with the hydrophobic sizing agent has a surface energy of about 20 dynes/cm2 to about 65 dynes/cm2. The therapeutic formulation includes salicylic acid or a pharmaceutically acceptable salt thereof present in about 0.5 wt. % to about 2.0 wt. % of the therapeutic formulation, a solvent that dissolves the salicylic acid, and a pressure sensitive adhesive.
The present invention also provides another adhesive patch. The adhesive patch includes a flexible backing having a front side and a back side. A therapeutic formulation is positioned on at least a portion of the front side of the backing, in at least a portion of the front side of the backing, or on and in at least a portion of the front side of the backing. At least a portion of the backing is treated with a hydrophobic sizing agent such that the portion of the backing treated with the hydrophobic sizing agent has a surface energy of about 20 dynes/cm2 to about 65 dynes/cm2. The therapeutic formulation includes a topical acne drug and a hot melt adhesive.
The therapeutic formulation can be partially embedded in at least a portion of the front side of the backing. The therapeutic formulation can be located on the entire surface of the front side of the backing. The backing can be porous. The backing can be vapor permeable. Upon contact with skin, the backing can retain the therapeutic formulation while the patch allows moisture from the skin to pass. The backing can include water insoluble material. The backing can have a thickness of about 0.025 mm to about 1.25 mm. The backing can include a nonwoven fabric. The backing can include polycellulose fibers, polyester fibers, polyurethane fibers, polyolefin fibers, polyamide fibers, cotton fibers, copolyester fibers, or any mixture thereof.
The hydrophobic sizing agent can be a fluorocarbon solution, a silicone-containing compound, or a combination thereof. The backing that is treated with the fluorocarbon solution can be Vilmed M1585 W/HY, Vilmed M1585H/HY, Vilmed M1586 W/HY, Vilmed M1586 H/HY, Vilmed M1570, Vilmed M 1573 F, Vilmed M 1573 FH, Vilmed M 1577 F, Vilmed M 1578 F, Vilmed M 1578 FH, or a combination thereof. The silicone-containing compound can be a polydimethyl siloxane, a dialkylsiloxane, a dimethylsiloxo vinyl alkene, a dialkylsiloxo vinyl alkene, a dimethylsiloxo acrylate, a dialkylsiloxo acrylate, a vinyl terminated polydimethylsiloxane, a vinyl terminated polydialkylsiloxane, or a combination thereof. At least a portion of the front side of the backing treated with the sizing agent. The entire surface of the front side of the backing can be treated with the sizing agent. The entire backing can be treated with the sizing agent. The sizing agent can be partially embedded in the backing.
The topical acne drug can be salicylic acid, resorcinol, resorcinol acetate, benzoyl peroxide, sulfur, retinol, retinoic acid, citric acid, an alpha hydroxy acid, retinal, a pharmaceutically acceptable salt thereof, or any combination thereof. The topical acne drug can be salicylic acid or a pharmaceutically acceptable salt thereof. The salicylic acid or the pharmaceutically acceptable salt thereof can be present in about 0.5 wt. % to about 2.0 wt. % of the therapeutic formulation. The sulfur can be present in about 3.0 wt. % to about 10.0 wt. % of the therapeutic formulation.
The solvent can include a polyhydric alcohol, water, or a combination thereof. The polyhydric alcohol can be propylene glycol, ethylene glycol, or a combination thereof. The propylene glycol can be present in about 3.0 wt. % to about 11.0 wt. % of the therapeutic formulation. The water can be present in about 2.0 wt. % to about 20.0 wt. % of the therapeutic formulation. The solvent can be present in about 6.0 wt. % to about 24.0 wt. % of the therapeutic formulation.
The therapeutic formulation can further include a filler. The filler can be malto dextrin. The malto dextrin can be present in about 1.0 wt. % to about 10.0 wt. % of the therapeutic formulation. The pressure sensitive adhesive can include one or more acrylic ester copolymers. The one or more acrylic ester copolymers can be present in about 3.0 wt. % to about 20.0 wt. % of the therapeutic formulation. The acrylic ester copolymer can be present in about 5.0 wt. % to about 15.0 wt. % of the therapeutic formulation. The adhesive can be positioned on the entire front side of the backing. The adhesive can be positioned on a portion of front side of the backing. The adhesive can be partially embedded in at least a portion of the backing.
The pressure sensitive adhesive can further include glycerin. The glycerin can be present in about 25.0 wt. % to about 70.0 wt. % of the therapeutic formulation. The glycerin can be present in about 45.0 wt. % to about 55.0 wt. % of the therapeutic formulation. The pressure sensitive adhesive can include an emulsifier. The emulsifier can be pectin. The pectin can be present in about 2.0 wt. % to about 10.0 wt. % of the therapeutic formulation.
The pressure sensitive adhesive can include a compound that provides structure and strength to the pressure sensitive adhesive or to the therapeutic formulation. The compound that provides structure and strength to the pressure sensitive adhesive or to the therapeutic formulation can be karaya, a polyacrylamide, xanthum gum, guar gum, a natural polymer, a synthetic polymer, a hydrophilic polymer, a hydrocolloidal polymer, starch, a starch derivative, vinyl acetate copolymer, polyvinyl pyrrolidone, polyethylene oxide, algin, derivatives of algin, a polyacrylate, polymaleic acid, polymaleic anhydride, a polyurethane, a polyurea, gum acacia, locust bean gum, modified guar gum, maltodextrin, carboxymethyl cellulose, carboxypropyl cellulose, polyvinyl alcohol, poly AMPS or a mixture thereof. The compound that provides structure and strength to the pressure sensitive adhesive or to the therapeutic formulation can be polyacrylamide. The polyacrylamide can be present in about 8.0 wt. % to about 30.0 wt. % of the therapeutic formulation. The compound that provides structure and strength to the pressure sensitive adhesive or to the therapeutic formulation can be karaya. The karaya can be present in about 8.0 wt. % to about 40.0 wt. % of the therapeutic formulation. The compound that provides structure and strength to the pressure sensitive adhesive or to the therapeutic formulation can be a combination of polyacrylamide and karaya.
The pressure sensitive adhesive can be located on the entire portion of the front side of the backing. The therapeutic formulation can further include a skin conditioner. The skin conditioner can be calamine, aloe, lanolin, glycerin, Vitamin E, Vitamin E acetate, farnesol, glycyrrhetinic acid, or any combination thereof. The aloe can be present in about 0.01 wt. % to about 2.0 wt. % of the therapeutic formulation. The Vitamin E acetate can be present in about 0.01 wt. % to about 2.0 wt. % of the therapeutic formulation.
The therapeutic formulation can further include one or more antimicrobial agents. The antimicrobial agent can be a xcex2-lactam compound, an aminoglycoside, or an antifungal agent. The antimicrobial agent can be erythromycin, tetracycline, clindamycin, or cephalosporin. The therapeutic formulation can further include one or more antiseptic agents. The antiseptic agent can be triclosan, phenoxy isopropanol, chlorhexidine gluconate, povidone iodine, or any combination thereof.
The adhesive patch can have a thickness of about 0.20 mm to about 0.75 mm. The adhesive patch can further include a release liner that is mounted on the front side of the backing. More than one patch can be mounted on the release liner. About 2 to about 20 adhesive patches are mounted on the release liner. The adhesive patch can be crescent, circular, or oval. The adhesive patch can have a diameter of about 0.1 inch to about 1.0 inch.
The portion of the backing treated with the hydrophobic sizing agent can have a surface energy of about 27 dynes/cm2 to about 56 dynes/cm2. The entire surface of the backing can be treated with the hydrophobic sizing agent. The hydrophobic sizing agent can penetrate at least a portion of the underlying surface of the backing. The hydrophobic sizing agent can penetrate the entire underlying surface of the backing.
The present invention also provides a method for treating or preventing acne or a pimple in a mammal (e.g., human) in need thereof. The method includes applying to the skin surface of the mammal having the acne or the pimple or the skin surface of the mammal at risk thereof an adhesive patch of the present invention for an effective period of time effective to treat or prevent acne or a pimple. The skin surface of the mammal having the acne or pimple or the skin surface of the mammal at risk thereof can be the face, neck, shoulder, chest, back, or any combination thereof. The effective period of time can be about one hour to about 12 hours.
The present invention also provides a method for exfoliating the skin surface of a mammal (e.g., human). The method includes applying to the skin surface of the mammal in need of such exfoliation an adhesive patch of the present invention. The adhesive patch is applied for an effective period of time after which the adhesive patch is removed, thereby effectively exfoliating the skin surface. The effective period of time can be about one second to about 12 hours.